Lithium Hydroxide → 2-((3R,5R,6S)-5-(3-Chlorophenyl)-6-(4-chlorophenyl)-3-methyl-2-oxo-1-((S)-1-(trifluoromethylsulfonamido)butan-2-yl)piperidin-3-yl)acetic acid

HRID 1048449Notes

Reaction equation

HRID 1048449 reaction equation
ClC1C=C([C@@H]2[C@@H](C3C=CC(Cl)=CC=3)N([C@@H](CC)CO)C(=O)[C@](CC(OC)=O)(C)C2)C=CC=1.C(P(CCCC)(CCCC)=CC#N)CCC.FC(F)(F)S(N)(=O)=O.[Cl:57][C:58]1[CH:59]=[C:60]([C@@H:64]2[C@@H:69]([C:70]3[CH:75]=[CH:74][C:73]([Cl:76])=[CH:72][CH:71]=3)[N:68]([C@@H:77]([CH2:87][CH3:88])[CH2:78][NH:79][S:80]([C:83]([F:86])([F:85])[F:84])(=[O:82])=[O:81])[C:67](=[O:89])[C@:66]([CH2:91][C:92]([O:94]C)=[O:93])([CH3:90])[CH2:65]2)[CH:61]=[CH:62][CH:63]=1.[Li+].[OH-]>C1(C)C=CC=CC=1.C(O)C>[Cl:57][C:58]1[CH:59]=[C:60]([C@@H:64]2[C@@H:69]([C:70]3[CH:71]=[CH:72][C:73]([Cl:76])=[CH:74][CH:75]=3)[N:68]([C@@H:77]([CH2:87][CH3:88])[CH2:78][NH:79][S:80]([C:83]([F:86])([F:85])[F:84])(=[O:82])=[O:81])[C:67](=[O:89])[C@:66]([CH2:91][C:92]([OH:94])=[O:93])([CH3:90])[CH2:65]2)[CH:61]=[CH:62][CH:63]=1

Participants

8

Reactant 5

HCID 3939Lithium HydroxideHCID 79001TrifluoromethylsulfonamideHCID 4622928CyanomethylenetributylphosphoraneHCID 58573771Methyl 2-((3R,5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-((S)-1-hydroxybutan-2-yl)-3-methyl-2-oxopiperidin-3-yl)acetateHCID 67998602methyl 2-((3R,5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-3-methyl-2-oxo-1-((S)-1-(trifluoromethylsulfonamido)butan-2-yl)piperidin-3-yl)acetate

Product 1

HCID 585732772-((3R,5R,6S)-5-(3-Chlorophenyl)-6-(4-chlorophenyl)-3-methyl-2-oxo-1-((S)-1-(trifluoromethylsulfonamido)butan-2-yl)piperidin-3-yl)acetic acid

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 1140TolueneSolvent

Conditions

Temperature
110 °C

Procedure

A reaction vial under argon was charged with methyl 2-((3R,5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-((S)-1-hydroxybutan-2-yl)-3-methyl-2-oxopiperidin-3-yl)acetate (0.048 g, 0.1 mmol; Example 186, Step A), 2-(tributylphosphoranylidene)acetonitrile (0.036 g, 0.15 mmol) and trifluoromethanesulfonamide (0.022 g, 0.15 mmol) in toluene (0.5 mL). The reaction mixture in the reaction vial was sealed and stirred at 110° C. for 1 h. Column chromatography on silica gel gave a mixture of methyl 2-((3R,5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-3-methyl-2-oxo-1-((S)-1-(trifluoromethylsulfonamido)butan-2-yl)piperidin-3-yl)acetate with an unknown impurity. This mixture was hydrolyzed with LiOH (1N solution in water, 0.3 mL) in ethanol (0.5 mL) for 3 h at rt. HPLC purification (C18 column, eluted with 10 to 95% CH3CN in water, with 0.1% TFA) gave the title compound.

Workup

  1. customA reaction vial under argon
  2. customThe reaction mixture in the reaction
  3. customvial was sealed
  4. customColumn chromatography on silica gel gave
  5. customHPLC purification (C18 column, eluted with 10 to 95% CH3CN in water, with 0.1% TFA)

Sources & evidence

ORD record
ord-edb8d9fa8b2942c583b937db37f1439e
Source dataset
uspto-grants-2013_10
Patent number
US08569341B2

Reaction notes

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